Storage and delivery containers for imaging and spectroscopic agents

ABSTRACT

A container for a polarizable gas includes an elongate container sheet having a laminate of a sealing layer and a barrier layer, a sealed container cavity defined by the container sheet by perimetrically sealing the sealing layer upon itself so as to enclose the container cavity, and a quantity of a polarizable gas within the container cavity. A method of evacuating the polarzable gas from the container includes evacuating the passageway of a fitting attached to the container prior to puncturing the container and evacuating its contents through the fitting.

FIELD OF THE INVENTION

[0001] The present invention relates to the field of the storage containers. More specifically, the present invention is directed to a storage and delivery container for a polarizable gas.

BACKGROUND OF THE INVENTION

[0002] The use of hyperpolarized gases for ex-vivo and in-vivo imaging is well known. As models for the widespread distribution of hyperpolarized gas doses become better defined, it is clear that a system providing for point-of-use polarization of gases be developed. In order to decrease the risk of waste, it is desirable to provide a unit-dose container for a polarizable gas which may be delivered to an imaging center and used on a per-patient basis. Moreover, a method for dispensing the contents of the container must ensure the gas contents do not become contaminated with ambient air.

[0003] The present invention addresses the need in the art for a unit-dose container for a hyperpolarizable gas which maintains the integrity of a dose through both storage and discharge.

SUMMARY OF THE INVENTION

[0004] The present invention addresses the needs of the art by providing a container for a polarizable gas formed from an elongate container sheet having a laminate of a sealing layer and a barrier layer. A sealed container cavity is defined by the container sheet by perimetrically sealing the sealing layer upon itself so as to enclose the container cavity. A quantity of a polarizable gas is provided within the container cavity.

[0005] The containers of the present invention are contemplated to provide a unit dose of a polarizable gas useful for hyperpolarized gas imaging and spectroscopic applications as is known with conventional magnetic resonance imaging (MRI) equipment. The containers desirably enclose approximately 0.5 liters of a gas at atmospheric pressure with sufficient capacity to accommodate thermal expansion of the gas without causing the container to rupture.

[0006] The containers are formed from a multilaminate barrier sheet material for maximizing shelf-life. The barrier sheets desirably include a layer for providing scratch resistance to the container, a metallic layer for preventing permeation of the gas from the container, and a layer for allowing easy sealing of the container.

[0007] The containers of the present invention may further include a connector fitting affixed to the barrier material for interfacing with a gas extraction device. The connector fitting defines an elongate fitting passageway through which the gas contents of the container may be evacuated. The connector fittings desirably do not penetrate the metallic layer of the multilaminate barrier sheet material so as not to degrade the blocking characteristics of the material. The connector is desirably bonded or heat-sealed to the outside of the container during manufacturing. Puncture of the container for extraction of the gas contents may be accomplished through the connector fitting.

[0008] The containers of the present invention may be attached to an evacuation device which engages the connector fitting in a fluid-tight manner. The fitting passageway is first evacuated of any contaminating gases prior to puncturing the container and evacuating the gas contents through the fitting passageway. Desirably, the container is punctured through the fitting passageway.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009]FIG. 1 depicts a first container of the present invention.

[0010]FIGS. 2A and 2B depict alternate multilaminate barriers of the containers of the present invention.

[0011] FIGS. 3-4 depict another container of the present invention.

[0012]FIG. 5 depicts yet another container of the present invention.

[0013]FIG. 6 depicts still another container of the present invention.

[0014]FIG. 7 depicts a gas loading system adapted for the container of FIG. 5.

[0015]FIG. 8 depicts still yet another container of the present invention.

[0016]FIG. 9 depicts a gas loading system adapted for the container of FIG. 7.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] As shown in FIG. 1, the present invention provides a container 10 for storing and delivering a mixture having a polarizable gas such as 3He or 129Xe. The container is generally a bag or soft container and is desirably formed from any material suitable for the purpose of storing the gas prior to its polarization. Container 10 is scalable so as to hold any size of a pre-selected dose of the polarizable gas. Each dose of the polarizable gas is contemplated to include some amount of another gas, such as N₂. For example, by way of illustration and not of limitation, each container of the present invention may hold a 0.5 liter gas mixture which comprises 99.25% 3He and 0.75% N₂.

[0018] Container 10 is desirably formed by a single elongate sheet 12 of container material and, optionally, an attached fitting 14. Container sheet 12 is folded about a transversely-extending crease area 16 so that the overlapping perimetrical edges of sheet 12 may be welded together to form a partial perimetrical seam 18 extending between opposed ends 16 a and 16 b of crease area 16. Container sheet 12 thereby defines an enclosed container cavity 20 for storing a dose of polarizable gas. The present invention contemplates that Fitting 14 may be adhered or bonded to an outside surface 12 a of container 10 so as to provide an adaptor for establishing fluid communication between cavity 20 and the polarization region of a polarizer device, not shown. The present invention further contemplates that container 10 may be formed from a fully perimetrical weld of a first and second container sheet 12 positioned in facing opposition so as to form enclosed cavity 20.

[0019] As shown in FIG. 2A, sheet 12 is desirably formed from a multilayer laminate made from, as viewed from cavity 20 to outside surface 12 a, at least a sheet of polyethylene 13 and a sheet of aluminum foil 15. The present invention further contemplates including layers of polyester and PET in constituting sheet 12. A polyethylene is desirably provided to form the interior layer of container 10 so as to ensure sealing of cavity 20 by perimetrical seam 18. The aluminum layer is contemplated to act as a barrier for the hyperpolarizable gas. It is further contemplated to metalize a polyethylene or polyester layer so as to provide for both heat sealing and gas barrier. With additional reference to FIG. 2B, another polyester layer 19, such as polyvinylidene chloride, is further contemplated for providing improved tear or puncture resistance. A PET layer 13 is contemplated to provide improved scratch or abrasion resistance. The present invention further contemplates alternate combinations of the order and location of the laminated layers may be provided to form sheet 12.

[0020] Fitting 14 is desirably formed from a suitable plastic material and includes an elongate cylindrical wall 22 defining an elongate passageway 24 extending between opposed wall ends 26 and 28. Fitting 14 desirably includes an annular flange 30 extending about second end 28 of cylindrical wall 22 so as to provide a larger surface area for bonding to outside surface 12 a of container sheet 12. Annular flange 30 may either define a central opening exposing surface 12 a to passageway 24 or may be a solid member which further isolates passagway 24 from surface 12 a. The means for affixing fitting 14 to sheet 12 desirably does not penetrate the aluminum layer 15 so as to minimize permeation of the stored gas therepast. It is contemplated that cylindrical wall 22 may be formed with luer-lock means extending either outwardly therefrom or inwardly into passageway 24 for engaging a complimentary fitting on a polarizer. Outwardly-projecting lugs 25 and 27 may be employed for this purpose. The polarizer into which the gas contents are delivered is equipped with the ability to first evacuate passageway 24 and then both puncture container 10 and evacuate cavity 20. In embodiments of the present invention lacking the attached fitting 14, the present invention contemplates that the polarizer will incorporate the means for providing a fluid-tight and evacuated attachment to fitting 14 as well as the means to puncture container sheet 12 and evacuate cavity 20.

[0021] Additional steps in the construction and filling of container 10 will be apparent from the descriptions hereinbelow.

[0022]FIGS. 3 and 4 depict a second container 110 of the present invention. Container 110 is desirably formed from a single elongate container sheet 112 and, optionally, a fitting 114. Container sheet 112 and fitting 114 are similar to sheet 12 and fitting 14 as previously described whereby like numbering describes like features. Container sheet 112 is folded about a crease 116 and the overlying edges are welded together so as to form a partial perimetrical seam 118 bounded by crease 116. Sheet 112 thereby provides a container cavity 120 for storing a dose of polarizable gas.

[0023] As shown in FIG. 4, container sheet 112 and seam 118 form an open inlet port 125 defining an inlet passagway 130 in fluid communication with cavity 120. The polarizable gas is introduced into cavity 120 through passageway 130. The present invention contemplates that a fluid-tight seal may be established between a filling device, not shown, and container 110 at inlet port 125. Container 110 will undergo at least one cycle of receiving a purge gas, such as N₂, through passageway 130 followed by a vacuum extraction of the contents of cavity 120 through passageway 130. It is desirable to evacuate all of the oxygen and other gases which may be entrapped in cavity 120 during the fabrication process. After undergoing the desired number of purge/vacuum cycles, the filling device will then deliver the polarizable gas through passageway 130 into cavity 120. While maintaining a fluid tight engagement about inlet port 125, seam 118 is completed across passageway 130 so as to isolate cavity 120 from the outside environment.

[0024]FIG. 5 depicts yet another container 210 of the present invention. Container 210 is formed from a container sheet 212 and, optionally, a closed fitting 214. Container sheet 212 is similar to sheet 12 as previously described whereby like numbering describes like features. Container sheet 212 is folded about a crease 216 such that overlying edges thereof may be welded together to form a partial perimetrical seam 218 and thereby define an enclosed container cavity 220. Cavity 220 is sized to contain a dose of polarizable gas for use in an imaging or spectrographic procedure. Seam 218 may be formed having a large enough surface area to accommodate various markers or indicia such as lables or bar codes. Container 210 is desirably formed having an inlet port 225 defining a passageway 230 in fluid communication with container cavity 220.

[0025] Container 210 is further shown incorporating sealed fitting 214 into seam 218. Sealed fitting 214 defines an elongate cylindrical fitting passageway 224 exteding in fluid communication with open end 226 thereof. Passageway 224 is in obstructed fluid communication with cavity 220. The present invention further contemplates affixing an adaptor, such as fitting 14, to the outside surface 212 a of container 210. It is also contemplated that passageway 224 will be evacuated of any contaminating gases prior to puncturing the closed end of fitting 214. Sealed fitting 214 may be punctured so as to render the contents of cavity 210 accessible for evacuation into a polarizer.

[0026]FIG. 6 depicts a dual-dose container 310 of the present invention. A dual-dose container is intended to provide enough polarizable gas for performing a full imaging or spectrometry procedure for a patient. Container 310 is desirably formed by perimetrically and transversely welding a first and second container sheet 312 and 312′ together. Perimetrical seam 318 and transverse seam 319 define first and second enclosed cavities 320 and 320′ therebetween. Cavities 320 and 320′ are each sized to contain a single dose of a polarizable gas. Container 310 is shown as providing first and second open inlet ports 325 and 325′ as interruptions in seam 318 so as to define first and second passageways in fluid communication with first and second cavities 320 and 320′, respectively. Once cavities 320 and 320′ have been evacuated and filled an appropriate number of times to ensure contaminant gases have been removed therefrom, the polarizable gas may be delivered thereto through ports 325 and 325′, respectively. Then, prior to fully disengaging the filling device from the container, seam 318 may be completed so as to isolate ports 325 and 325′, thereby rendering cavities 320 and 320′ closed. Seam 318 also incorporates elongate fittings 314 and 314′, which are similar to fitting 214 in design and operation.

[0027]FIG. 8 shows a gas loading system 500 for filling dual-dose container 310. Gas loading system 500 includes a cannister supply 501 of N₂ and a hyperpolarizable gas. Gas loading system 500 further includes first and second gas injector probes 502 and 504 receivable in inlet ports 325 and 325′, respectively. Gas loading system further includes means for maintaining a fluid tight connection between probes 502 and 504 and inlet ports 325 and 325′ while performing both the purge and evacuation cycles and the sealing of the inlet ports after filling cavities 320 and 320′ with the polarizable gas.

[0028]FIG. 9 depicts a unit-dose cylinder 610 of the present invention. Cylinder 610 provides a rigid container for transporting a hyperpolarizable gas. The contents of cylinder 610 may be dispensed into a flexible gas container of the present invention. Cylinder 610 is desirably formed from aluminum or stainless steel. Cylinder 610 includes an outer container wall 612 having an open end 614 covered by a puncturable cover 615. Container wall 612 defines and interior cavity 616, in fluid communication with open end 614. Open end 614 may further include therein a poppet-type or ball-type valve for controlling the introduction and evacuation of gases into and out from cavity 616. It is further contemplated that container wall 612 is annularly scored or weakened about open end 614 where cylinder 610 may be opened.

[0029]FIG. 8 depicts a gas loading system 700 adapted for filling a unit-dose container of the present invention. Gas loading system 700 includes a rotary turntable 702 for accommodating a number of unit-dose cylinders 610 thereon. Turntable 702 positions each end 614 of cylinder 610 in underlying spaced registry below an extraction nozzle 704. Extraction nozzle 704 may be extended into sealed contact about end 614 of a cylinder 610 and includes the means to purge the void extending between the openable end of the cylinder and a gas delivery valve within fill nozzle 704. Fill nozzle 704 includes the means for purging oxygen from the void prior to communicating with cavity 616 and extracting the polarizable gas mixture therefrom. The polarizable gas mixture may include, for purposes of illustration and not of limitation, a polarizable gas and N₂. Gas loading system 700 also includes means for filling a flexible container of the present invention as previously described.

[0030] While the particular embodiment of the present invention has been shown and described, it will be obvious to those skilled in the art that changes and modifications may be made without departing from the teachings of the invention. The matter set forth in the foregoing description and accompanying drawings is offered by way of illustration only and not as a limitation. The actual scope of the invention is intended to be defined in the following claims when viewed in their proper perspective based on the prior art. 

What is claimed is:
 1. A container for a polarizable gas comprising: an elongate container sheet comprising a laminate of a sealing layer and a barrier layer; a sealed container cavity defined by said container sheet by perimetrically sealing said sealing layer upon itself so as to enclose said container cavity; and a quantity of a polarizable gas within said container cavity.
 2. The container of claim 1, wherein said container sheet further comprises a laminate of a metalized polymeric layer for providing both a heat sealable layer and a gas barrier for said polarizable gas.
 3. The container of claim 2, wherein said container sheet further comprises a laminate including a PET layer for providing abrasion resistance to the container.
 4. The container of claim 1, wherein said container cavity is further defined between said perimetrical seam extending between a substantially linear crease folded into said container sheet.
 5. The container of claim 1, wherein said container cavity is further defined between said container sheet and a second container sheet perimetrically sealed together.
 6. The container of claim 1, further comprising a mixture of said hyperpolarizable gas with a non-hyperpolarizable gas.
 7. The container of claim 6, wherein said mixture comprises approximately 99.25% 3He and approximately 0.75% N₂.
 8. The container of claim 1, further comprising a elongate fluid exchange fitting mounted upon an outside surface of said container sheet, said fitting being connectable to a gas withdrawal system for evacuating said mixture from said container cavity.
 9. A method for preparing an expandable storage container for receiving a quantity of hyperpolarizable gas, comprising the steps of: forming a container cavity with an elongate container sheet; perimetrically sealing said container cavity by joining the overlying perimetrical edges together about a fill port; providing a quantity of purge gas into the hyperpolarizable gas container through said fill port; expanding the hyperpolarized gas container by directing a quantity of purge gas therein; collapsing the hyperpolarized gas container by removing purge gas therefrom; filling said container cavity with a hyperpolarizable gas mixture; and sealing said fill port so as to provide a sealed container cavity holding said hyperpolarizable gas mixture.
 10. The method of claim 9, wherein said forming step further comprises forming said container cavity between a first and second container sheet.
 11. The method of claim 9, further comprising the step of attaching an evacuation fitting to an outside surface of said container, said fitting being connectable to a gas withdrawal system for evacuating said mixture from said container cavity.
 12. A method of withdrawing a polarizable gas mixture from a container holding the gas mixture, the container comprising an elongate container sheet comprising a laminate of a sealing layer and a barrier layer; a sealed container cavity defined by the container sheet by folding over the container sheet and perimetrically sealing the sealing layer upon itself so as to enclose the container cavity; and a quantity of a polarizable gas within the container cavity, the container further having a fitting affixed thereto, the fitting defining a passageway through which the gas mixture is to be evacuated, comprising the steps of: engaging the fitting with a dispense mechanism so as to form a fluid-tight seal therebetween; evacuating air from the fitting passageway; puncturing the container so that the fitting passageway is in unobstructed fluid communication with the container cavity; and evacuating the gas mixture from the container cavity through the fitting passageway.
 13. The method of claim 12, wherein said puncturing step further comprises the step of puncturing the container through the fitting passageway. 